Endoplasmic reticulum stress in disorders of myelinating cells

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Nat Neurosci. 2009 Mar 15.

Endoplasmic reticulum stress in disorders of myelinating cells

Lin W, Popko B.

Department of Cell Biology and Neuroscience, University of South Alabama,

Mobile, Alabama, USA.

Myelinating cells, oligodendrocytes in the CNS and Schwann cells in the

peripheral nervous system produce an enormous amount of plasma membrane during

the myelination process, making them particularly susceptible to disruptions of

the secretory pathway. Endoplasmic reticulum stress, initiated by the

accumulation of unfolded or misfolded proteins, activates the unfolded protein

response, which adapts cells to the stress.

If this adaptive response is insufficient, the unfolded protein response

activates an apoptotic program to eliminate the affected cells.

Recent observations suggest that endoplasmic reticulum stress in myelinating

cells is important in the pathogenesis of various disorders of myelin, including

Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher disease and Vanishing White

Matter Disease, as well as in the most common myelin disorder, multiple

sclerosis.

A better understanding of endoplasmic reticulum stress in myelinating cells has

laid the groundwork for the design of new therapeutic strategies for promoting

myelinating cell survival in these disorders.